This research focuses on the cellular and molecular processes that take place in hair cells of the sensory organs of the vestibular and auditory systems during development of the vertebrate ear. The aquatic amphibian, Xenopus laevis, will be used as a model system for the study of hair cells and their development. The broad objective of this research is to gain an integrated view of the development and proliferation of sensory hair cells of the internal ear, by using multidisciplinary approaches that draw on techniques from biophysics, anatomy, tissue culture, and molecular biology. Project goal are: (1) The patch clamp method will be used to determine the ionic mechanisms underlying signal transduction in Xenopus hair cells. Results of biophysical studies of hair cell electrical properties will be correlated with structural studies of hair cell morphology and stereociliary bundle characteristics during different stages of development. (2) Light, scanning, and transmission microscopy will be used to examine development of Xenopus hair cell structure and innervation. (3) Recombinant DNA technology will be used to clone genes for ion channels and cytoskeletal proteins expressed in Xenopus hair cells. (4) An in vitro culture preparation will be established and used for studies of hair cell regeneration. The knowledge gained from this research will advance understanding of normal vestibulo-auditory system function as well as dysfunction. Results will increase knowledge of signal transduction pathways in hair cells, and will reveal cellular and genetic events that underlie hair cell differentiation and development. An important long-term objective of this study is to understand the mechanisms that regulate hair cell proliferation and regeneration. The knowledge gained should prove useful in developing treatments for hearing disorders based on hair cell dysfunction, particularly those caused by trauma.